α-Tocopheryl succinate induces apoptosis in erbB2-expressing breast cancer cell via NF-κB pathway
Xiu-fang WANG1, Ying XIE, Hong-gang WANG
1Department of Genetics, Hebei Medical University, Hebei Key Lab of Laboratory Animal, Shijiazhuang 050017, China. wangxiufang@live.cn
Aim:
to study the molecular mechanisms underlying α-tocopheryl succinate (α-TOS)-induced apoptosis in erbB2-positive breast cancer cells and to determine whether α-TOS and the human recombinant TNF-related apoptosis-inducing ligand (hrTRAIL) act synergically to induce cell death of erbB2-expressing breast cancer cells.
Methods:
the annexin V binding method was used to measure apoptosis induced by α-TOS and/or hrTRAIL. RT-PCR and Western blotting were performed to detect gene and protein expression. A colorimetric assay was performed to detect caspase activity. The TransAM(TM) NF-κB p65 kit was used to assess NF-κB activation.
Results:
α-TOS (100 μmol/L) significantly inhibited NF-κB nuclear translocation in erbB2-expressing breast cancer cells; this inhibition is expected to result in the inactivation of NF-κB. α-TOS (50 and 100 μmol/L) inhibited the expression of Flice-like inhibitory protein (FLIP) and cellular inhibitor of apoptosis protein 1 (c-IAP1) in erbB2-positive cells. α-TOS (100 μmol/L) inhibited Akt activation and augmented the activity of caspase 3 and caspase 8 in breast cancer cells expressing erbB2. α-TOS (50 μmol/L) and hrTRAIL (30 mg/mL) acted synergically to induce apoptosis in breast cancer cells. α-TOS also decreased the hrTRAIL-induced transient activation of NF-κB .
Conclusion:
our results suggest that α-TOS mediates the apoptosis of erbB2-positive breast cancer cells and acts synergically with hrTRAIL via the NF-κB pathway.
Insights
Alpha-tocopheryl succinate (α-TOS) induces apoptosis in erbB2-positive breast cancer cells by inhibiting NF-κB signaling. α-TOS synergizes with hrTRAIL to enhance cancer cell death.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer, particularly erbB2-positive subtypes, remains a significant health concern.
- Targeting apoptosis pathways is a key strategy in cancer therapy.
- Understanding the molecular mechanisms of novel therapeutic agents is crucial.
Purpose of the Study:
- To elucidate the molecular mechanisms of alpha-tocopheryl succinate (α-TOS)-induced apoptosis in erbB2-positive breast cancer cells.
- To investigate the synergistic effects of α-TOS and human recombinant TNF-related apoptosis-inducing ligand (hrTRAIL) on erbB2-expressing breast cancer cell death.
Main Methods:
- Apoptosis was measured using the annexin V binding assay.
- Gene and protein expression were analyzed via RT-PCR and Western blotting.
- Caspase activity and NF-κB activation were assessed using colorimetric assays and a specific NF-κB p65 kit.
Main Results:
- α-TOS inhibited NF-κB nuclear translocation, FLIP, c-IAP1, and Akt activation in erbB2-positive breast cancer cells.
- α-TOS treatment augmented caspase 3 and caspase 8 activity.
- A combination of α-TOS and hrTRAIL demonstrated synergistic induction of apoptosis and reduced hrTRAIL-induced NF-κB activation.
Conclusions:
- α-TOS effectively mediates apoptosis in erbB2-positive breast cancer cells.
- α-TOS and hrTRAIL act synergistically to induce cancer cell death, primarily through the NF-κB pathway.
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